Breast cancer is the most prevalent cancer among women in the US. A non-invasive, highly reliable and accurate biomarker panel is needed for this growing population of women at high risk for breast cancer recurrence and second primary cancers. Metalloproteinase levels in urine are directly correlated with progressing stages of breast cancer among women. All prior studies have been conducted using cross- sectional data and thus, unable to establish a temporal relationship between the biomarker and disease. In this proposed project, we will evaluate for the first time, whether metalloproteinase levels in urine samples obtained prior to diagnosis are related to the development of breast cancer. We will use a nested case-control study of 470 incident breast cancer cases and 940 individually matched controls within the Singapore Chinese Health Study, a population-based prospective cohort. There is strong experimental evidence for the role of matrix metalloproteinases in early breast tumorigenesis, and in the angiogenic switch that may result a subgroup of dysplasia/carcinoma in situ that is prone to progression toward invasive disease. Our goal is to establish whether a urinary metalloproteinase panel can be used as a biomarker for assessing breast cancer risk, and ultimately result in fewer women dying from breast cancer. PUBLIC HEALTH RELEVANCE: The proposed project will determine whether levels of metallo-proteinases in urine can predict the development of breast cancer. The results from this project have the potential to substantially reduce breast cancer mortality with a non-invasive, urine-based marker of early disease.